```

[Federal Register Volume 89, Number 249 (Monday, December 30, 2024)]
[Proposed Rules]
[Pages 106384-106393]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-30798]

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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-1457]

Schedules of Controlled Substances: Placement of Seven Specific 
Fentanyl-Related Substances in Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Notice of proposed rulemaking.

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SUMMARY: The Drug Enforcement Administration proposes placing seven 
fentanyl-related substances, as identified in this proposed rule, in 
schedule I of the Controlled Substances Act. These seven substances 
fall within the definition of fentanyl-related substances set forth in 
the February 6, 2018 temporary scheduling order. Through the Temporary 
Reauthorization and Study of Emergency Scheduling of Fentanyl Analogues 
Act, which became law on February 6, 2020, Congress extended the 
temporary control of fentanyl-related substances until May 6, 2021. 
This temporary order was subsequently extended multiple times, most 
recently on December 29, 2022, through the Consolidated Appropriations 
Act, 2023, which extended the order until December 31, 2024. If 
finalized, this action would make permanent the existing regulatory 
controls and administrative, civil, and criminal sanctions applicable 
to schedule I controlled substances on persons who handle (manufacture, 
distribute, import, export, engage in research, conduct instructional 
activities or chemical analysis, or possess), or propose to handle 
these seven specific controlled substances.

DATES: Comments must be submitted electronically or postmarked on or 
before January 29, 2025.
    Interested persons may file a request for a hearing or waiver of 
hearing pursuant to 21 CFR 1308.44 and in accordance with 21 CFR 
1316.47 and/or 1316.49, as applicable. Requests for a hearing, and 
waivers of an opportunity for a hearing or to participate in a hearing, 
must be received on or before January 29, 2025.

ADDRESSES: Interested persons may file written comments on this 
proposal in accordance with 21 CFR 1308.43(g). To ensure proper 
handling of comments, please reference ``Docket No. DEA-1457'' on all 
electronic and written correspondence, including any attachments.
     Electronic comments: The Drug Enforcement Administration 
(DEA) encourages commenters to submit all comments electronically 
through the Federal eRulemaking Portal which provides the ability to 
type short comments directly into the comment field on the web page or 
to attach a file for lengthier comments. Please go to https://www.regulations.gov and follow the online instructions at that site for 
submitting comments. Upon completion of your submission, you will 
receive a Comment Tracking Number for your comment. Submitted comments 
are not instantaneously available for public view on Regulations.gov. 
If you have received a Comment Tracking Number, your comment has been 
successfully submitted and there is no need to resubmit the same 
comment. Commenters should be aware that the electronic Federal Docket 
Management System will not accept comments after 11:59 p.m. Eastern 
Time on the last day of the comment period.
     Paper comments: Paper comments that duplicate electronic 
submissions are not necessary. Should you wish to mail a paper comment 
in lieu of an electronic comment, it should be sent via regular or 
express mail to: Drug Enforcement Administration, Attn: DEA Federal 
Register Representative/DPW, 8701 Morrissette Drive, Springfield, 
Virginia 22152.
     Hearing requests: All requests for a hearing and waivers 
of participation, together with a written statement of position on the 
matters of fact and law asserted in the hearing, must be filed with the 
DEA Administrator, who will make the determination of whether a hearing 
will be needed to address such matters of fact and law in the 
rulemaking. Such requests must be sent to: Drug Enforcement 
Administration, Attn: Administrator, 8701 Morrissette Drive, 
Springfield, Virginia 22152. For informational purposes, a courtesy 
copy of requests for hearing and waivers of participation should also 
be sent to: (1) Drug Enforcement Administration, Attn: Hearing Clerk/
OALJ, 8701 Morrissette Drive, Springfield, Virginia 22152; and (2) Drug 
Enforcement Administration, Attn: DEA Federal Register Representative/
DPW, 8701 Morrissette Drive, Springfield, Virginia 22152.
     Paperwork Reduction Act Comments: All comments concerning 
collections of information under the Paperwork Reduction Act must be 
submitted to the Office of Information and Regulatory Affairs, OMB, 
Attention: Desk Officer for DOJ, Washington, DC 20503. Please state 
that your comment refers to Docket No. DEA-1457.

FOR FURTHER INFORMATION CONTACT: Dr. Terrence L. Boos, Drug and 
Chemical

[[Page 106385]]

Evaluation Section, Diversion Control Division, Drug Enforcement 
Administration; Telephone: (571) 362-3249.

SUPPLEMENTARY INFORMATION: In this proposed rule, the Drug Enforcement 
Administration (DEA) proposes to permanently schedule the following 
seven controlled substances in schedule I of the Controlled Substances 
Act (CSA), including their isomers, esters, ethers, salts, and salts of 
isomers, esters, and ethers whenever the existence of such isomers, 
esters, ethers, and salts is possible within the specific chemical 
designation:
     para-chlorofentanyl (N-(4-chlorophenyl)-N-(1-
phenethylpiperidin-4-yl)propionamide),
     ortho-chlorofentanyl (N-(2-chlorophenyl)-N-(1-
phenethylpiperidin-4-yl)propionamide),
     meta-fluorofuranyl fentanyl (N-(3-fluorophenyl)-N-(1-
phenethylpiperidin-4-yl)furan-2-carboxamide),
     ortho-methylcyclopropyl fentanyl (N-(2-methylphenyl)-N-(1-
phenethylpiperidin-4-yl)cyclopropanecarboxamide),
     beta-methylacetyl fentanyl (N-phenyl-N-(1-(2-
phenylpropyl)piperidin-4-yl)acetamide),
     tetrahydrothiofuranyl fentanyl (N-(1-phenethylpiperidin-4-
yl)-N-phenyltetrahydrothiophene-2-carboxamide),
     para-fluoro valeryl fentanyl (N-(4-fluorophenyl)-N-(1-
phenethylpiperidin-4-yl)pentanamide).

Posting of Public Comments

    All comments received in response to this docket are considered 
part of the public record. DEA will make comments available for public 
inspection online at https://www.regulations.gov, unless reasonable 
cause is given. Such information includes personal or business 
identifiers (such as name, address, state of federal identifiers, etc.) 
voluntarily submitted by the commenter.
    Commenters submitting comments which include personal identifying 
information (PII), confidential, or proprietary business information 
that the commenter does not want made publicly available should submit 
two copies of the comment. One copy must be marked ``CONTAINS 
CONFIDENTIAL INFORMATION'' and should clearly identify all PII or 
business information the commenter does not want to be made publicly 
available, including any supplemental materials. DEA will review this 
copy, including the claimed PII and confidential business information, 
in its consideration of comments. The second copy should be marked ``TO 
BE PUBLICLY POSTED'' and must have all claimed confidential PII and 
business information already redacted. DEA will post only the redacted 
comment on https://www.regulations.gov for public inspection. DEA 
generally will not redact additional information contained in the 
comment marked ``TO BE PUBLICLY POSTED.'' The Freedom of Information 
Act applies to all comments received.
    For easy reference, an electronic copy of this document and 
supplemental information to this proposed scheduling action are 
available at https://www.regulations.gov.

Request for Hearing or Appearance; Waiver

    Pursuant to 21 U.S.C. 811(a), this action is a formal rulemaking 
``on the record after opportunity for a hearing.'' Such proceedings are 
conducted pursuant to the provisions of the Administrative Procedure 
Act (APA), 5 U.S.C. 551-559.\1\ Interested persons, as defined in 21 
CFR 1300.01(b), may file requests for a hearing in conformity with the 
requirements of 21 CFR 1308.44(a) and 1316.47(a), and such requests 
must:
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    \1\ 21 CFR 1308.41 through 1308.45; 21 CFR part 1316, subpart D.
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    (1) state with particularity the interest of the person in the 
proceeding;
    (2) state with particularity the objections or issues concerning 
which the person desires to be heard; and
    (3) state briefly the position of the person with regard to the 
objections or issues.
    Any interested person may file a waiver of an opportunity for a 
hearing or to participate in a hearing in conformity with the 
requirements of 21 CFR 1308.44(c), together with a written statement of 
position on the matters of fact and law involved in any hearing.\2\
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    \2\ 21 CFR 1316.49.
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    All requests for a hearing and waivers of participation, together 
with a written statement of position on the matters of fact and law 
involved in such hearing, must be sent to DEA using the address 
information provided above. The decision whether a hearing will be 
needed to address such matters of fact and law in the rulemaking will 
be made by the Administrator. If a hearing is needed, DEA will publish 
a notification of hearing on the proposed rulemaking in the Federal 
Register.\3\ Further, once the Administrator determines a hearing is 
needed to address such matters of fact and law in rulemaking, she will 
then designate an Administrative Law Judge (ALJ) to preside over the 
hearing. The ALJ's functions shall only commence upon designation, as 
provided in 21 CFR 1316.52.
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    \3\ 21 CFR 1308.44(b), 1316.53.
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    In accordance with 21 U.S.C. 811 and 812, the purpose of a hearing 
would be to determine whether para-chlorofentanyl, ortho-
chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-methylcyclopropyl 
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, 
and para-fluoro valeryl fentanyl meet the statutory criteria for 
placement in schedule I, as proposed in this rule.

Legal Authority

    The CSA provides that proceedings for the issuance, amendment, or 
repeal of the scheduling of any drug or other substance may be 
initiated by the Attorney General (delegated to the Administrator of 
DEA pursuant to 28 CFR 0.100) on his own motion, at the request of the 
Secretary of Health and Human Services (HHS), or on the petition of an 
interested party.\4\ This proposed action is initiated on the 
Administrator's own motion and supported by, inter alia, a 
recommendation from the Assistant Secretary for Health of HHS 
(Assistant Secretary for HHS or Assistant Secretary) and an evaluation 
of all other relevant data by DEA. If finalized, this action would make 
permanent the existing temporary regulatory controls and 
administrative, civil, and criminal sanctions of schedule I controlled 
substances on any person who handles or proposes to handle these seven 
substances.
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    \4\ 21 U.S.C. 811(a).
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Background

    On February 6, 2018, pursuant to 21 U.S.C. 811(h)(1), DEA published 
an order in the Federal Register (83 FR 5188) temporarily placing 
fentanyl-related substances, as defined in that order, in schedule I of 
the CSA based upon a finding that these substances pose an imminent 
hazard to the public safety.\5\ As discussed below in Factor 3, the 
seven substances named in this proposed rule meet the existing 
definition of fentanyl-related substances as they are not otherwise 
controlled in any other schedule (i.e., not included under another DEA 
Controlled Substance Code Number) and are structurally related to 
fentanyl by one or more of the five modifications listed under the 
definition. That temporary

[[Page 106386]]

order was effective upon the date of publication. Pursuant to 21 U.S.C. 
811(h)(2), the temporary control of fentanyl-related substances, a 
class of substances as defined in the order, as well as the seven 
specific substances already covered by that order, was set to expire on 
February 6, 2020. However, on February 6, 2020, as explained in DEA's 
April 10, 2020 correcting amendment),\6\ Congress extended that 
expiration date until May 6, 2021, by enacting the Temporary 
Reauthorization and Study of the Emergency Scheduling of Fentanyl 
Analogues Act.\7\ This temporary order was subsequently extended 
multiple times, most recently on December 29, 2022, through the 
Consolidated Appropriations Act, 2023,\8\ which extended the order 
until December 31, 2024. Consequently, the temporary control of these 
seven substances will remain in effect until December 31, 2024, unless 
it is extended. Accordingly, as published elsewhere in this issue of 
the Federal Register, the DEA Administrator is ordering an extension of 
this temporary order as it relates to these seven substances.
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    \5\ Schedules of Controlled Substances: Temporary Placement of 
Fentanyl-Related Substances in Schedule I, 83 FR 5188 (Feb. 6, 
2018).
    \6\ Schedules of Controlled Substances: Temporary Placement of 
Fentanyl-Related Substances in Schedule I; Correction, 85 FR 20155 
(Apr. 10, 2020).
    \7\ Public Law 116-114, sec. 2, 134 Stat. 103.
    \8\ Public Law 117-328, division O, title VI, sec. 601.
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    The Administrator, on her own motion pursuant to 21 U.S.C. 811(a), 
is initiating proceedings to permanently schedule para-chlorofentanyl, 
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl in 
schedule I of the CSA. Pursuant to 21 U.S.C. 811(b), DEA gathered the 
necessary data and reviewed the available information regarding the 
pharmacology, chemistry, trafficking, actual abuse, pattern of abuse, 
and the relative potential for abuse for these substances. On April 3, 
2023, in accordance with 21 U.S.C. 811(b), the Administrator submitted 
a request to the Assistant Secretary to provide DEA with a scientific 
and medical evaluation of available information and a scheduling 
recommendation for these seven substances.
    On October 25, 2024, the Assistant Secretary submitted HHS's 
scientific and medical evaluation and scheduling recommendation for 
para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl and 
their salts to the Administrator. The Secretary recommended placing 
these seven fentanyl related substances in schedule I of the CSA. In 
accordance with 21 U.S.C. 811(c), upon receipt of the scientific and 
medical evaluation and scheduling recommendation from HHS, DEA reviewed 
the documents and all other relevant data and conducted its own eight-
factor analysis of the abuse potential of these seven substances.

Proposed Determination To Permanently Schedule Seven Specific Fentanyl-
Related Substances

    As discussed in the background section, the Administrator is 
initiating proceedings, pursuant to 21 U.S.C. 811(a), to permanently 
add para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl 
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl to 
schedule I. DEA reviewed the scientific and medical evaluation and 
scheduling recommendation received from HHS, and all other relevant 
data and conducted its own eight-factor analysis of the abuse potential 
of these seven substances pursuant to 21 U.S.C. 811(c). Included below 
is a brief summary of each factor as analyzed by HHS and DEA, and as 
considered by DEA in its proposed scheduling action. Readers should 
refer to the full eight-factor analyses prepared by HHS and by DEA in 
support of this proposal, which are available in their entirety under 
``Supporting Documents'' of the public docket for this proposed rule at 
https://www.regulations.gov under Docket Number ``DEA-1457.''

1. The Drug's Actual or Relative Potential for Abuse

    In addition to considering the information HHS provided in its 
scientific and medical evaluation document for these seven fentanyl-
related substances, DEA also considered all other relevant data 
regarding actual or relative potential for abuse of these three 
substances. The term ``abuse'' is not defined in the CSA; however, the 
legislative history of the CSA suggests that DEA consider the following 
criteria when determining whether a particular drug or substance has a 
potential for abuse: \9\
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    \9\ Comprehensive Drug Abuse Prevention and Control Act of 1970, 
H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 (1970); reprinted in 1970 
U.S.C.C.A.N. 4566, 4603.
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    (a) There is evidence that individuals are taking the drug or drugs 
containing such a substance in amounts sufficient to create a hazard to 
their health or to the safety of other individuals or to the community; 
or
    (b) There is significant diversion of the drug or drugs containing 
such a substance from legitimate drug channels; or
    (c) Individuals are taking the drug or drugs containing such a 
substance on their own initiative rather than on the basis of medical 
advice from a practitioner licensed by law to administer such drugs in 
the course of his professional practice; or
    (d) The drug or drugs containing such a substance are new drugs so 
related in their action to a drug or drugs already listed as having a 
potential for abuse to make it likely that the drug will have the same 
potentiality for abuse as such drugs, thus making it reasonable to 
assume that there may be significant diversions from legitimate 
channels, significant use contrary to or without medical advice, or 
that it has a substantial capability of creating hazards to the health 
of the user or to the safety of the community.
    Law enforcement seizure data indicate that individuals have and are 
using para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl 
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, 
and para-fluoro valeryl fentanyl on their own initiative rather than on 
the basis of medical advice from a practitioner licensed by law to 
administer such drugs in the course of his professional practice, 
especially since there is no currently accepted medical use for these 
seven substances. According to the National Forensic Laboratory 
Information System (NFLIS-Drug) \10\ database, which collects drug 
identification results from drug cases submitted to and analyzed by 
Federal, State, and local forensic laboratories, there have been 214 
reports for para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl 
between 2020 and 2024. According to HHS, para-

[[Page 106387]]

chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-
fluoro valeryl fentanyl are not legally marketed as drugs in the United 
States or anywhere else in the world. These substances have no approved 
medical use other than their limited use in scientific research. As 
such, the legal sources of the substances are limited to legitimate 
chemical companies supplying them for scientific research.
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    \10\ The National Forensic Laboratory Information System (NFLIS) 
represents an important resource in monitoring illicit drug 
trafficking, including the diversion of legally manufactured 
pharmaceuticals into illegal markets. NFLIS is a comprehensive 
information system that includes data from forensic laboratories 
that handle more than 96% of an estimated 1.0 million distinct 
annual State and local drug analysis cases. NFLIS includes drug 
chemistry results from completed analyses only. While NFLIS data is 
not direct evidence of abuse, it can lead to an inference that a 
drug has been diverted and abused. See Schedules of Controlled 
Substances: Placement of Carisoprodol Into Schedule IV, 76 FR 77330, 
77332 (Dec. 12, 2011). NFLIS data were queried November 1, 2024.
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    para-Chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl 
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, 
and para-fluoro valeryl fentanyl are not approved for medical use and 
are not formulated or approved for clinical use. As such, all use is on 
an individual's own initiative, rather than on the basis of medical 
advice from a practitioner licensed by law to administer drugs. Law 
enforcement seizures and case reports demonstrate that individuals are 
taking these seven fentanyl-related substances on their own initiative, 
rather than on the basis of medical advice from a licensed 
practitioner.
    Based on available data, para-chlorofentanyl, ortho-chlorofentanyl, 
meta-fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro 
valeryl fentanyl, are related in their effects to the actions of other 
mu-opioid receptor (MOR) agonists,\11\ such as fentanyl, that are 
already listed as having potential for abuse. Because high doses of MOR 
agonists can produce respiratory depression leading to death, these 
fentanyl-related substances at high doses have substantial capability 
of creating hazards to the health of the user or to the safety of the 
community. According to HHS, these seven fentanyl-related substances 
exert their actions at least in part through the MOR and thus have a 
high likelihood of having substantially similar potential for abuse as 
other schedule I opioids. Both DEA's and HHS's eight-factor analyses 
found that the abuse potential of these substances is similar to other 
schedule I opioids and presents a hazard to the health and safety of 
individuals and the community.
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    \11\ Drug Enforcement Administration-Veterans Affairs (DEA-VA) 
Interagency Agreement. Binding and Functional Activity at Delta, 
Kappa and Mu Opioid Receptors. In Vitro Receptor and Transporter 
Assays for Abuse Liability Testing for the DEA by the VA 
(unpublished data).
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2. Scientific Evidence of the Drug's Pharmacological Effects, if Known

    According to DEA and HHS, the pharmacological activity of these 
substances in humans is unknown. Data obtained from preclinical studies 
show that these fentanyl-related substances (para-chlorofentanyl, 
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl) 
exhibit a pharmacological profile similar to that of fentanyl, 
morphine, and several schedule I opioid substances that are 
structurally related to fentanyl. Similar to fentanyl and other 
structurally related synthetic opioids, fentanyl-related substances 
namely para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl 
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl have 
been shown to bind to the mu-opioid receptors with varying 
affinities.\12\ Also, similar to fentanyl and other structurally 
related synthetic opioids, these seven fentanyl-related substances 
behave as agonists at the MOR sites in in vitro functional studies.
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    \12\ in vitro Pharmacology data was collected through DEA--
Veterans Affairs interagency agreement: ``in vitro Receptor and 
Transporter Assays for Abuse Liability Testing for the DEA by the 
VA''.
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    Studies conducted to examine the antinociceptive effect of the 
seven fentanyl-related substances in a warm water tail-withdrawal assay 
and their mediation by opioid receptors as determined by naltrexone 
antagonism showed these seven fentanyl-related substances, similar to 
fentanyl and morphine, produced antinociceptive effects as measured by 
an increase in tail withdrawal latency.\13\ Pre-treatment with 
naltrexone, an opioid receptor antagonist, attenuated antinociceptive 
effects of the seven-fentanyl related substances. These data 
demonstrate that similar to morphine and fentanyl, para-chlorofentanyl, 
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, para-fluoro valeryl fentanyl produced 
dose-dependent antinociception in the warm-water tail-withdrawal assay 
that can be attenuated by naltrexone pre-treatment.
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    \13\ Gatch MB. (2024). Test of analgesic effects alone and in 
combination with naltrexone. 15DDHQ19F00001173, ``Evaluation of 
Abuse Potential of Synthetic Opioids Using in Vivo Pharmacological 
Studies'' (unpublished data).
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    There is a strong correlation between the discriminative stimulus 
effects of a given drug in animals and its subjective effects in 
humans.\14\ Data from drug discrimination studies \15\ show that the 
seven-fentanyl related substances fully and dose-dependently substitute 
for the discriminative stimulus effects produced by morphine in Sprague 
Dawley rats trained to discriminate 3.2 mg/kg morphine from saline.\16\ 
These data demonstrate para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro 
valeryl fentanyl, similar to morphine (schedule II) and fentanyl 
(schedule II), are mu-opioid receptor agonists.
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    \14\ Solinas M, Panlilio LV, Justinova Z, Yasar S, Goldberg SR. 
(2006). Using drug-discrimination techniques to study the abuse-
related effects of psychoactive drugs in rats. Nat Protoc.1(3):1194-
206.
    \15\ Drug discrimination is widely used to determine whether a 
new test drug or substance is pharmacologically similar to a known 
drug of abuse.
    \16\ DEA-Synthetic Opioids Purchase Agreement (2022-2024). 
Evaluation of synthetic opioid substances using analgesia and the 
drug discrimination assay. In Vivo Testing for the DEA by Gatch 
(Univ. of North Texas).
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3. The State of Current Scientific Knowledge Regarding the Drug or 
Other Substance

    para-Chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl 
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl are 
synthetic opioids in the 4-anilidopiperidine structural class which 
includes fentanyl. As defined in the February 6, 2018 temporary 
scheduling order, fentanyl-related substances include any substance not 
otherwise controlled in any schedule (i.e., not included under any 
other Administration Controlled Substance Code Number) that is 
structurally related to fentanyl by one or more of the following 
modifications:
    (A) Replacement of the phenyl portion of the phenethyl group by any 
monocycle, whether or not further substituted in or on the monocycle;
    (B) substitution in or on the phenethyl group with alkyl, alkenyl, 
alkoxyl, hydroxyl, halo, haloalkyl, amino or nitro groups;
    (C) substitution in or on the piperidine ring with alkyl, alkenyl, 
alkoxyl, ester, ether, hydroxyl, halo, haloalkyl, amino or nitro 
groups;
    (D) replacement of the aniline ring with any aromatic monocycle, 
whether

[[Page 106388]]

or not further substituted in or on the aromatic monocycle; and/or
    (E) replacement of the N-propionyl group by another acyl group.
    [GRAPHIC] [TIFF OMITTED] TP30DE24.017
    
Figure 1: Regions of the Chemical Structure of Fentanyl Described in 
The Definition of a Fentanyl-Related Substance

    According to the February 6, 2018 temporary scheduling order, the 
existence of a substance with anyone, or any combination, of above-
mentioned modifications (see figure 1) would meet the structural 
requirements of the definition of fentanyl-related substances. The 
present seven substances fall within the definition of fentanyl-related 
substances by the following modifications:
    1. para-chlorofentanyl: substitution on the aniline ring (meets 
definition for modification D);
    2. ortho-chlorofentanyl: substitution on the aniline ring (meets 
definition for modification D);
    3. meta-fluorofuranyl fentanyl: substitution on the aniline ring 
and replacement of the N-propionyl group with another acyl group (meets 
definition for modifications D and E);
    4. ortho-methylcyclopropyl fentanyl: substitution on the aniline 
ring and replacement of the N-propionyl group with another acyl group 
(meets definition for modifications D and E);
    5. beta-methylacetyl fentanyl: substitution on the phenethyl group 
with an alkyl group and replacement of the N-propionyl group with 
another acyl group (meets definition for modifications B and E);
    6. tetrahydrothiofuranyl fentanyl: replacement of the N-propionyl 
group with another acyl group (meets definition for modification E);
    7. para-fluoro valeryl fentanyl: substitution on the aniline ring 
and replacement of the N-propionyl group with another acyl group (meets 
definition for modifications D and E).

4. Its History and Current Pattern of Abuse

    Evidence suggests that the pattern of abuse of para-chlorofentanyl, 
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl 
parallels that of prescription opioid analgesics. Currently, the United 
States is in the midst of an illicit opioid abuse epidemic. There has 
been a marked increase in the encounters of synthetic opioids that are 
structurally related to fentanyl that parallels an increase in deaths 
related to synthetic opioids. Thus, the recreational abuse of fentanyl-
like substances continues to be a significant concern. These substances 
are distributed to users, often with unpredictable outcomes. para-
Chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-
fluoro valeryl fentanyl have been encountered by law enforcement 
officials.
    Law enforcement encountered these seven substances in the United 
States. According to the NFLIS \17\ database, 214 reports were 
registered containing six of the substances (para-chlorofentanyl, 
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, beta-methylacetyl 
fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl 
fentanyl) from state or local forensic laboratories from 2020 to 2024. 
ortho-Methylcyclopropyl fentanyl was not specifically listed in the 
NFLIS database, although in 2018, there were three reports of 
methylcyclopropyl fentanyl.
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    \17\ NFLIS data were queried November 1, 2024. NFLIS data 
reporting is still pending for 2023 and 2024 due to normal lag time.
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5. The Scope, Duration, and Significance of Abuse

    The rapid appearance of fentanyl-related substances presents 
numerous challenges for forensic and toxicology laboratories. The 
identification of a new substance requires full structural elucidation, 
sometimes requiring specialized instrumentation not available to all 
forensic laboratories. Laboratories are required to quickly adapt 
testing procedures to identify new substances. It remains likely that 
the prevalence of these substances in opioid related emergency room 
admissions and deaths is underreported as standard immunoassays may not 
differentiate fentanyl from substances structurally related to 
fentanyl.
    The population likely to abuse fentanyl-related substances overlaps 
with the population abusing prescription opioid analgesics, heroin, 
fentanyl, and other synthetic opioid substances. Because abusers of 
fentanyl-related substances are likely to obtain these substances 
through unregulated sources, the identity, purity, and quantity are 
uncertain and inconsistent, thus posing significant adverse health 
risks to the end user. The misuse and abuse of opioids have been 
demonstrated and are well characterized. According to the most recent 
data from the National Survey on Drug Use and Health (NSDUH) \18\ of 
the Substance Abuse and Mental Health Services Administration 
(SAMHSA),\19\ in 2023, an estimated 8.9 million people aged 12 or older 
misused opioids in the past year, including 8.6 million prescription 
pain reliever misusers and 660,000 heroin users. In 2023, among people 
aged 12 or older, 828,000 people misused fentanyl in the past year. 
NSDUH data show that among people aged 12 or older in 2023, 627,000 
people used illicitly manufactured fentanyl in the past year. This 
population is likely to be at risk of abusing fentanyl-related 
substances. Individuals who initiate (i.e., use a drug for the first 
time) use of fentanyl-related substances are likely to be at risk of 
developing substance use disorder, overdose, and death, similar to the 
risks of other opioid analgesics (e.g., fentanyl, morphine, etc.).
---------------------------------------------------------------------------

    \18\ The National Survey on Drug Use and Health, formerly known 
as the National Household Survey on Drug Abuse (NHSDA), is conducted 
annually by the Department of Health and Human Services Substance 
Abuse and Mental Health Services Administration (SAMHSA). It is the 
primary source of estimates of the prevalence and incidence of 
nonmedical use of pharmaceutical drugs, illicit drugs, alcohol, and 
tobacco use in the United States. The survey is based on a 
nationally representative sample of the civilian, non-
institutionalized population 12 years of age and older. The survey 
excludes homeless people who do not use shelters, active military 
personnel, and residents of institutional group quarters such as 
jails and hospitals. The NSDUH provides yearly national and state 
level estimates of drug abuse, and includes prevalence estimates by 
lifetime (i.e., ever used), past year and past month abuse or 
dependence.
    \19\ The Substance Abuse and Mental Health Services 
Administration (SAMHSA) is a branch of the U.S. Department of Health 
and Human Services (HHS). It is charged with improving the quality 
and availability of prevention, treatment, and rehabilitative 
services in order to reduce illness, death disability, and cost to 
society resulting from substance abuse and mental illness.
---------------------------------------------------------------------------

    According to HHS, it is highly likely that the prevalence of these 
fentanyl-related substances in emergency room admissions and fatalities 
is under reported because standard immunoassays may not be sufficient 
to distinguish between fentanyl and

[[Page 106389]]

substances that are structurally related to fentanyl. Law enforcement 
reports demonstrate para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro 
valeryl fentanyl are being illicitly distributed and abused. The use of 
these seven fentanyl-related substances is likely to increase the 
scope, duration, and significance of abuse based on their 
pharmacological similarity to drugs that are abused in the current 
opioid epidemic (e.g., fentanyl).

6. What, if Any, Risk There Is to the Public Health

    The increase in opioid overdose deaths in the United States has 
been exacerbated by the availability of potent synthetic opioids such 
as fentanyl and numerous other structurally related substances in the 
illicit drug market.\20\ These substances have a history of being 
trafficked as replacements for other opioids, such as heroin and other 
synthetic opioids. Fentanyl is a potent synthetic opioid that is 
primarily prescribed for acute and chronic pain and is approximately 
100 times more potent than morphine. As such, fentanyl has a high risk 
of abuse, dependence and overdose that can lead to death. Because 
fentanyl-related substances have a similar chemical structure to 
fentanyl, these substances are expected to have similar biological 
effects. Indeed, these seven fentanyl-related substances produced 
pharmacological effects similar to fentanyl. The adverse effects of 
substances structurally related to fentanyl on humans are largely 
identical to those of fentanyl and other opioid analgesics. These 
fentanyl-related substances pose the same qualitative public health 
risks as heroin, fentanyl, and other opioid analgesic substances. The 
DEA Toxicology Testing Program (DEA-Tox) \21\ identified three drug 
paraphernalia where para-chlorofentanyl was detected. These cases 
occurred between May 2022 and June 2024. As the data demonstrate, the 
potential for overdoses exists for these substances and these 
substances pose risk to public health.
---------------------------------------------------------------------------

    \20\ Centers for Disease Control and Prevention, (2024, April). 
Understanding the opioid overdose epidemic. https://www.cdc.gov/overdose-prevention/about/understanding-the-opioid-overdoseepidemic.html Spencer, M. R., Warner, M., Cisewski, J. A., 
Mini[ntilde]o, A., Dodds, D., Perera, J., & Ahmad, F. B., Estimates 
of drug overdose deaths involving fentanyl, methamphetamine, 
cocaine, heroin, and oxycodone: United States, 2021. Vital 
Statistics Rapid Release (Report No. 27). National Center for Health 
Statistics; Zibbell, J. E., Aldridge, A., Grabenauer, M., Heller, 
D., Duhart Clarke, S., Pressley, D., & Smiley-McDonald, H. (2023). 
Associations between opioid overdose deaths and drugs confiscated by 
law enforcement and submitted to crime laboratories for analysis, 
United States, 2014-2019: An observational study. The Lancet 
Regional Health--Americas, 25.
    \21\ DEA-TOX is a DEA-run program whereby unused biological 
samples from victims of drug overdoses can be extensively tested for 
the presence of novel psychoactive substances, in addition to other 
drugs of abuse.
---------------------------------------------------------------------------

    According to HHS, the lack of hospitalization or fatality for these 
seven fentanyl-related substances is not surprising because the enzyme 
linked immunosorbent assay (ELISA) which is used to detect fentanyl 
cross-reacts with fentanyl-related substances when fentanyl is present 
above a threshold level.\22\ Thus, fatalities that might be associated 
with the fentanyl-related substances may be underreported. As with any 
opioid not approved for medical use, the health and safety risks for 
users are high. Public health data suggest that para-chlorofentanyl, 
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl may be 
a direct risk to public health.
---------------------------------------------------------------------------

    \22\ Guerrieri D, Kjellqvist F, Kronstrand R, Gr[eacute]en H. 
(2019). Validation and Cross-Reactivity Data for Fentanyl Analogs 
with the Immunalysis Fentanyl ELISA. J Anal Toxicol. 43(1):18-24.
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7. Its Psychic or Physiological Dependence Liability

    According to HHS, the psychic or physiologic dependence of these 
seven fentanyl-related substances has not been studied in clinical 
studies and is therefore unknown. HHS notes that pharmacology data for 
these substances as MOR agonists with known abuse potential 
demonstrates their property of producing physical and psychic 
dependence similar to other MOR agonists. The discontinuation of the 
use of MOR agonists, such as morphine and fentanyl (Schedule II drugs), 
is associated with withdrawal symptoms indicative of physical 
dependence. Opioid withdrawal syndrome is characterized by central 
nervous system irritability, gastrointestinal dysfunction, yawning, 
diaphoresis, and fever.\23\ Thus, the pharmacological similarity and 
pattern of abuse of para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro 
valeryl fentanyl are indicative of their potential to possess a psychic 
and physiological dependence liability similar to that of other mu 
opioid receptor agonist substances, such as heroin and fentanyl.
---------------------------------------------------------------------------

    \23\ Katz R, Kelly W, Hsi A. (1994). Prospective-study on the 
occurrence of withdrawal in critically ill children who receive 
fentanyl by continuous-infusion. Critical Care Medicine 16:763-767.
---------------------------------------------------------------------------

8. Whether the Substance is an Immediate Precursor of a Substance 
Already Controlled Under the CSA

    para-Chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl 
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl are 
not immediate precursors of any controlled substance of the CSA, as 
defined by 21 U.S.C. 802(23).
    Conclusion: Based on consideration of the scientific and medical 
evaluation and accompanying recommendation of HHS, and on DEA's own 
eight-factor analysis, DEA finds that these facts and all relevant data 
constitute substantial evidence of potential for abuse of para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl. As 
such, DEA proposes to permanently schedule these seven substances as 
controlled substances under the CSA.

Proposed Determination of Appropriate Schedule

    The CSA establishes five schedules of controlled substances known 
as schedules I, II, III, IV, and V. The CSA also outlines the findings 
required to place a drug or other substance in any particular 
schedule.\24\ After consideration of the analysis and recommendation of 
the Assistant Secretary for HHS and review of all other available data, 
the Administrator of DEA, pursuant to 21 U.S.C. 811(a) and 812(b)(1), 
finds that:
---------------------------------------------------------------------------

    \24\ See 21 U.S.C. 812(b).
---------------------------------------------------------------------------

    (1) para-Chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl 
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl, 
similar to fentanyl, are mu-opioid receptor agonists. The seven 
fentanyl-related substances have analgesic effects, and these effects 
are mediated by [mu]-opioid receptor agonism. These substances that 
produce mu-opioid receptor agonist effects in the CNS are considered as 
having a high potential for abuse (e.g. morphine and fentanyl). Data 
obtained from drug discrimination studies indicate that para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl

[[Page 106390]]

fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, 
and para-fluoro valeryl fentanyl fully substituted for the 
discriminative stimulus effects of morphine. Thus, these substances 
have a high potential for abuse.
    (2) There is no FDA-approved drug application for para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl in the 
United States. Further, there are no adequate and well-controlled 
clinical studies for any of these substances, and there are no well-
defined finished dosage forms for any of these fentanyl-related 
substances. There are no known therapeutic applications for these seven 
fentanyl-related substances, and thus they have no currently accepted 
medical use in the United States.\25\
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    \25\ Pursuant to 21 U.S.C. 812(b)(1)(B), when placing a drug or 
substance in schedule I of the CSA, DEA must consider whether the 
substance has a currently accepted medical use in treatment in the 
United States. First, DEA looks to whether the drug or substance has 
FDA approval. When no FDA approval exists, DEA has traditionally 
applied a five-part test to a drug or substance to determine whether 
a drug or substance has a currently medical use: i. the drug's 
chemistry must be known and reproducible; ii. there must be adequate 
safety studies; iii. there must be adequate and well-controlled 
studies proving efficacy; iv. the drug must be accepted by qualified 
experts; and v. the scientific evidence must be widely available. 
Marijuana Scheduling Petition; Denial of Petition; Remand, 57 FR 
10499 (Mar. 26, 1992), pet. for rev. denied, Alliance for Cannabis 
Therapeutics v. Drug Enforcement Admin., 15 F.3d 1131, 1135 (D.C. 
Cir. 1994). DEA applied the traditional five-part test and concluded 
the test was not satisfied. In a recent published letter in a 
different context, HHS applied an additional two-part test to 
determine currently accepted medical use for substances that do not 
satisfy the five-part test: (1) whether there exists widespread, 
current experience with medical use of the substance by licensed 
health care providers operating in accordance with implemented 
jurisdiction-authorized programs, where medical use is recognized by 
entities that regulate the practice of medicine, and, if so, (2) 
whether there exists some credible scientific support for at least 
one of the medical conditions for which part (1) is satisfied. On 
April 11, 2024, the Department of Justice's Office of Legal Counsel 
(OLC) issued an opinion, which, among other things, concluded that 
HHS's two-part test would be sufficient to establish that a drug has 
a currently accepted medical use. Office of Legal Counsel, 
Memorandum for Merrick B. Garland Attorney General Re: Questions 
Related to the Potential Rescheduling of Marijuana at 3 (April 11, 
2024). In its eight-factor assessment, HHS determined that these 
seven fentanyl-related substances did not satisfy this two-part 
test. Therefore, since both DEA and HHS have determined that these 
seven fentanyl-related substances do not satisfy the five-part test, 
and HHS has determined that these seven fentanyl-related substances 
do not satisfy the additional two-part test, DEA concludes that 
para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl 
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl 
fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl 
fentanyl do not have a currently accepted medical use.
---------------------------------------------------------------------------

    (3) There is a lack of accepted safety for use of para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl under 
medical supervision. Because these seven substances have no FDA-
approved medical use and have not been investigated as new drugs, their 
safety for use under medical supervision has not been determined. 
Therefore, there is a lack of accepted safety for use of these seven 
substances under medical supervision.
    Based on these findings, the Administrator of DEA concludes that 
para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl, 
including their isomers, esters, ethers, salts, and salts of isomers, 
esters, and ethers whenever the existence of such isomers, esters, 
ethers, and salts is possible within the specific chemical designation, 
warrant continued control in schedule I of the CSA.\26\
---------------------------------------------------------------------------

    \26\ 21 U.S.C. 812(b)(1).
---------------------------------------------------------------------------

Requirements for Handling para-Chlorofentanyl, ortho-Chlorofentanyl, 
meta-Fluorofuranyl fentanyl, ortho-Methylcyclopropyl fentanyl, beta-
Methylacetyl fentanyl, Tetrahydrothiofuranyl fentanyl, and para-Fluoro 
valeryl fentanyl

    As discussed above, these seven fentanyl-related substances are 
currently subject to a temporary scheduling order, which added them to 
schedule I. If this rule is finalized as proposed, para-chlorofentanyl, 
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl would 
be subject, on a permanent basis, to the CSA's schedule I regulatory 
controls and administrative, civil, and criminal sanctions applicable 
to the manufacture, distribution, dispensing, importing, exporting, 
research, and conduct of instructional activities, including the 
following:
    1. Registration. Any person who handles (manufactures, distributes, 
dispenses, imports, exports, engages in research, or conducts 
instructional activities or chemical analysis with, or possesses) para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl must 
be registered with DEA to conduct such activities pursuant to 21 U.S.C. 
822, 823, 957, and 958, and in accordance with 21 CFR parts 1301 and 
1312.
    2. Security. para-Chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro 
valeryl fentanyl are subject to schedule I security requirements and 
must be handled and stored pursuant to 21 U.S.C. 821, 823, and in 
accordance with 21 CFR 1301.71 through 1301.76. Non-practitioners 
handling these seven substances also must comply with the screening 
requirements of 21 CFR 1301.90 through 1301.93.
    3. Labeling and Packaging. All labels and labeling for commercial 
containers of para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro 
valeryl fentanyl must comply with 21 U.S.C. 825 and 958(e) and be in 
accordance with 21 CFR part 1302.
    4. Quota. Only registered manufacturers are permitted to 
manufacture para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro 
valeryl fentanyl in accordance with a quota assigned pursuant to 21 
U.S.C. 826 and in accordance with 21 CFR part 1303.
    5. Inventory. Any person registered with DEA to handle para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl must 
have an initial inventory of all stocks of controlled substances 
(including these substances) on hand on the date the registrant first 
engages in the handling of controlled substances pursuant to 21 U.S.C. 
827, and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
    After the initial inventory, every DEA registrant must take a new 
inventory of all stocks of controlled substances (including para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl) on 
hand

[[Page 106391]]

every two years pursuant to 21 U.S.C. 827 and 958(e) and in accordance 
with 21 CFR 1304.03, 1304.04, and 1304.11.
    6. Records and Reports. Every DEA registrant must maintain records 
and submit reports with respect to para-chlorofentanyl, ortho-
chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-methylcyclopropyl 
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, 
and para-fluoro valeryl fentanyl, pursuant to 21 U.S.C. 827, 832(a), 
and 958(e), and in accordance with 21 CFR 1301.74(b) and (c) and 
1301.76(b) and parts 1304, 1312, and 1317. Manufacturers and 
distributors would be required to submit reports regarding para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl to the 
Automation of Reports and Consolidated Order System pursuant 21 U.S.C. 
827, and in accordance with 21 CFR parts 1304 and 1312.
    7. Order Forms. Every DEA registrant who distributes para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl must 
comply with the order form requirements, pursuant to 21 U.S.C. 828 and 
21 CFR part 1305.
    8. Importation and Exportation. All importation and exportation of 
para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, 
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl, 
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl must 
be in compliance with 21 U.S.C. 952, 953, 957, and 958, and in 
accordance with 21 CFR part 1312.
    9. Liability. Any activity involving para-chlorofentanyl, ortho-
chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-methylcyclopropyl 
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, 
and para-fluoro valeryl fentanyl not authorized by, or in violation of, 
the CSA or its implementing regulations is unlawful, and may subject 
the person to administrative, civil, and/or criminal sanctions.

Regulatory Analyses

Executive Orders 12866, 13563, and 14094 (Regulatory Review)

    In accordance with 21 U.S.C. 811(a), this proposed scheduling 
action is subject to formal rulemaking procedures done ``on the record 
after opportunity for a hearing,'' which are conducted pursuant to the 
provisions of 5 U.S.C. 556 and 557. The CSA sets forth the criteria for 
scheduling a drug or other substance. Such actions are exempt from 
review by the Office of Management and Budget (OMB) pursuant to section 
3(d)(1) of Executive Order (E.O.) 12866 and the principles reaffirmed 
in E.O. 13563. E.O. 14094 modernizes the regulatory review process to 
advance policies that promote the public interest and address national 
priorities.

Executive Order 12988, Civil Justice Reform

    This proposed regulation meets the applicable standards set forth 
in sections 3(a) and 3(b)(2) of E.O. 12988 to eliminate drafting errors 
and ambiguity, minimize litigation, provide a clear legal standard for 
affected conduct, and promote simplification and burden reduction.

Executive Order 13132, Federalism

    This proposed rulemaking does not have federalism implications 
warranting the application of E.O. 13132. The proposed rule does not 
have substantial direct effects on the States, on the relationship 
between the National Government and the States, or the distribution of 
power and responsibilities among the various levels of government.

Executive Order 13175, Consultation and Coordination With Indian Tribal 
Governments

    This proposed rule does not have tribal implications warranting the 
application of E.O. 13175. It does not have substantial direct effects 
on one or more Indian tribes, on the relationship between the Federal 
Government and Indian tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian tribes.

Regulatory Flexibility Act

    The Administrator, in accordance with the Regulatory Flexibility 
Act, 5 U.S.C. 601-612, has reviewed this rule and by approving it, 
certifies that it will not have a significant economic impact on a 
substantial number of small entities. On February 6, 2018, DEA 
published an order to temporarily place fentanyl-related substances, as 
defined in the order, in schedule I of the CSA pursuant to the 
temporary scheduling provisions of 21 U.S.C. 811(h). However, as 
explained in DEA's April 10, 2020 correcting amendment,\27\ Congress 
extended that expiration date until May 6, 2021, by enacting the 
Temporary Reauthorization and Study of the Emergency Scheduling of 
Fentanyl Analogues Act.\28\ This temporary order was subsequently 
extended multiple times, most recently on December 29, 2022, through 
the Consolidated Appropriations Act, 2023,\29\ which extended the order 
until December 31, 2024. DEA estimates that all entities handling or 
planning to handle para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro 
valeryl fentanyl have already established and implemented systems and 
processes required to handle these substances which meet the definition 
of fentanyl-related substances.
---------------------------------------------------------------------------

    \27\ Schedules of Controlled Substances: Temporary Placement of 
Fentanyl-Related Substances in Schedule I; Correction, 85 FR 20155 
(Apr. 10, 2020).
    \28\ Public Law 116-114, sec. 2, 134 Stat. 103.
    \29\ Public Law 117-328, division O, title VI, sec. 601.
---------------------------------------------------------------------------

    There are currently 170 registrations authorized to specifically 
handle the fentanyl-related substances as a class, which include one or 
more of the following substances: para-chlorofentanyl, ortho-
chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-methylcyclopropyl 
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, 
and para-fluoro valeryl fentanyl, as well as a number of registered 
analytical labs that are authorized to handle schedule I controlled 
substances generally. Some of these entities are likely to be large 
entities. However, since DEA does not have information of registrant 
size, DEA conservatively assumes all of 170 registrants affected by 
this rule are small entities.
    A review of the 170 registrations indicates that all entities that 
currently handle para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro 
valeryl fentanyl also handle other schedule I controlled substances and 
have established and implemented (or maintained) systems and processes 
required to handle these substances. Therefore, DEA anticipates that 
this proposed rule will impose minimal or no economic impact on any 
affected entities; and thus, will not have a significant economic 
impact on any of the 95 affected small entities. Therefore,

[[Page 106392]]

DEA has concluded that this proposed rule will not have a significant 
economic impact on a substantial number of small entities.

Unfunded Mandates Reform Act of 1995

    In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995, 
2 U.S.C. 1501 et seq., DEA has determined and certifies that this 
action would not result in any Federal mandate that may result ``in the 
expenditure by State, local, and tribal governments, in the aggregate, 
or by the private sector, of $100,000,000 or more (adjusted annually 
for inflation) in any 1 year . . . .'' Therefore, neither a Small 
Government Agency Plan nor any other action is required under the UMRA 
of 1995.

Paperwork Reduction Act of 1995

    This proposed rule would not impose a new collection or modify an 
existing collection of information under the Paperwork Reduction Act of 
1995.\30\ Also, this proposed rule would not impose new or modify 
existing recordkeeping or reporting requirements on state or local 
governments, individuals, businesses, or organizations. However, this 
proposed rule would require compliance with the following existing OMB 
collections: 1117-0003, 1117-0004, 1117-0006, 1117-0008, 1117-0009, 
1117-0010, 1117-0012, 1117-0014, 1117-0021, 1117-0023, 1117-0029, and 
1117-0056. An agency may not conduct or sponsor, and a person is not 
required to respond to, a collection of information unless it displays 
a currently valid OMB control number.
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    \30\ 44 U.S.C. 3501-3521.
---------------------------------------------------------------------------

Signing Authority

    This document of the Drug Enforcement Administration was signed on 
December 19, 2024, by Administrator Anne Milgram. That document with 
the original signature and date is maintained by DEA. For 
administrative purposes only, and in compliance with requirements of 
the Office of the Federal Register, the undersigned DEA Federal 
Register Liaison Officer has been authorized to sign and submit the 
document in electronic format for publication, as an official document 
of DEA. This administrative process in no way alters the legal effect 
of this document upon publication in the Federal Register.

Heather Achbach,
Federal Register Liaison Officer, Drug Enforcement Administration.

List of Subjects in 21 CFR Part 1308

    Administrative practice and procedure, Drug traffic control, 
Reporting and recordkeeping requirements.

    For the reasons set out above, DEA proposes to amend 21 CFR part 
1308 as follows:

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

0
1. The authority citation for 21 CFR part 1308 continues to read as 
follows:

    Authority:  21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise 
noted.

0
2. In Sec.  1308.11:
0
a. Redesignate paragraphs (b)(104) through (109) as paragraphs (b)(111) 
through (116);
0
b. Redesignate paragraphs (b)(87) through (103) as paragraphs (b)(93) 
through (109);
0
c. Redesignate paragraphs (b)(84) through (86) as paragraphs (b)(89) 
through (91);
0
d. Redesignate paragraphs (b)(82) and (83) as paragraphs (b)(86) and 
(87);
0
e. Redesignate paragraphs (b)(76) through (81) as paragraphs (b)(79) 
through (84);
0
f. Redesignate paragraphs (b)(59) through (75) as paragraphs (b)(61) 
through (77);
0
g. Redesignate paragraphs (b)(21) through (58) as paragraphs (b)(22) 
through (59); and
0
h. Add new paragraphs (b)(21), (60), (78), (85), (88), (92), and (110).
    The additions read as follows:

Sec.  1308.11  Schedule I.

* * * * *
    (b) * * *

------------------------------------------------------------------------
 
------------------------------------------------------------------------
 
                              * * * * * * *
(21) beta-methylacetyl fentanyl (N-phenyl-N-(1-(2-                  9868
 phenylpropyl)piperidin-4-yl)acetamide).................
 
                              * * * * * * *
(60) meta-fluorofuranyl fentanyl (N-(3-fluorophenyl)-N-             9871
 (1-phenethylpiperidin-4-yl)furan-2-carboxamide)........
 
                              * * * * * * *
(78) ortho-chlorofentanyl (N-(2-chlorophenyl)-N-(1-                 9828
 phenethylpiperidin-4-yl)propionamide...................
 
                              * * * * * * *
(85) ortho-methylcyclopropyl fentanyl (N-(2-                        9849
 methylphenyl)-N-(1-phenethylpiperidin-4-
 yl)cyclopropanecarboxamide)............................
 
                              * * * * * * *
(88) para-chlorofentanyl (N-(4-chlorophenyl)-N-(1-                  9818
 phenethylpiperidin-4-yl)propionamide)..................
 
                              * * * * * * *
(92) para-fluoro valeryl fentanyl (N-(4-fluorophenyl)-N-            9870
 (1-phenethylpiperidin-4-yl)pentanamide)................
 
                              * * * * * * *
(110) tetrahydrothiofuranyl fentanyl (also known as:                9869
 tetrahydrothiophene fentanyl) (N-(1-phenethylpiperidin-
 4-yl)-N-phenyltetrahydrothiophene-2-carboxamide).......
 
                              * * * * * * *
------------------------------------------------------------------------

[[Page 106393]]

* * * * *
[FR Doc. 2024-30798 Filed 12-27-24; 8:45 am]
BILLING CODE 4410-09-P
```